Background: The senescence of the immune system is a complex phenomenon, characterized by impairment of several lymphocyte activities and generally considered a state of immune dysregulation. Aging is a condition associated with many social changes likely to induce psychological stress, which is often perceived as uncontrollable and can lead, in some cases, to clinically relevant depression. In the recent years a growing interest has been raised for the study of bidirectional interactions between the central nervous system and the immunological network (psychoneuroimmunology). Objective and Methods: We analyzed the possibility that chronic psychological distress and depression could worsen some immune functions in the aged. We postulate the neuroendocrine mechanisms of psychoimmune interaction, analyzing both the human and animal studies focused on aging. Results: The data from the literature reviewed suggest a significant impact of affective disorders on immune functions in the elderly subjects. This psychoimmune imbalance appears particularly important when the studies are carried out in otherwise healthy aged people. Conclusions: Here we reviewed the relationships between psychological stress and depression and immunological functions, with particular regard to those aspects pertinent to the aging process. The clinical relevance of these interactions remains to be elucidated, but the high frequency in the aged of autoimmune, infectious, and neoplastic diseases suggests to focus on the psychoneuroimmune interactions in the old age. We also propose some outlines for future studies concerning psychoneuroimmunology and aging.

Academic stress is a good model of psychological stress in humans for studying psychoneuroimmune correlations. We looked for correlations between psychological scores, immune tests and plasma levels of cortisol and neuropeptide Y (NPY). A group of medical students were evaluated at the beginning of the academic year (Baseline) and the day before an examination (Stress). They underwent evaluation by The Profile of Mood States (POMS), The Malaise Inventory, The Self Efficacy Scale and A Global Assessment of Recent Stress (GARS). The lymphocyte subsets, the lymphocyte proliferative response and the cytokine production were also evaluated. We detected modifications of some psychological test scores between the Baseline and Stress evaluation, a significant reduction of lymphocyte proliferation, IL-2 production and percentage of the lymphocyte CD19, and an increase in plasma cortisol levels during stress. The lymphocyte proliferation negatively correlated with the POMS score as well as the percentage of CD16+ cells with NPY plasma levels. NPY levels were not different from Baseline. The emotional and mood states seem to influence immunity.

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In patients affected with different tumours, disorders concerning clotting are frequently observed. The biological processes leading to coagulation are probably involved in the mechanisms of metastasis. We studied plasma levels of thrombin-antithrombin III complexes (TAT) in 90 patients affected with lung tumours subgrouped in small cell and non-small cell (NSC) lung cancer: 17 patients had no evidence of disease after surgery (NE); the remaining 73 patients were divided according to the absence (LOC) or the presence (META) of metastases. All the patients were followed up for several months. In all the lung cancer patient groups, at the beginning of the study we detected TAT levels that were higher than in controls. During the follow-up period, the NSC-NE patients with no recurrence of the disease as well as the NSC-LOC patients responding to the treatment had a decrease in TAT levels (p < 0.01 and p < 0.05, respectively). The NSC-META patients with progression of their disease had, in contrast, an increase in TAT levels (p < 0.01). Our data reveal the presence of ‘latent coagulation disorders’ as assessed by the presence of high TAT levels in the majority of lung cancer patients. The follow-up study indicates that in the NSC group, a relation exists between coagulation activation and rate of tumour progression and/or response to treatment. In cancer patients the early detection of coagulation disorders could also allow, therefore, the prevention of thromboembolism and/or haemorrhage by administration of appropriate treatment.